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1.
Sci Rep ; 14(1): 14131, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898131

RESUMO

To study the influence of pits on shock wave propagation and the propagation of shock waves within pits, numerical simulations were used to calculate the distribution of overpressure peak values at the bottom and rear of the pits at 5 depths and 5 explosion center distances. The results indicate that diffraction occurs when the explosion shock wave passes through the edge of the crater; The peak overpressure of the shock wave at the bottom of the pit exhibits a "spoon shaped" distribution, and the peak overpressure on the right side is significantly higher than that on the left side; There are two distinct boundary regions for the overpressure of the shock wave behind the crater due to the influence of the crater; The distance between the explosion centers has little effect on the distribution trend of the overpressure peak of the shock wave at the bottom and rear of the pit, mainly affecting the magnitude of the overpressure peak. The research results provide theoretical support for the analysis of the propagation law of explosion shock waves and guidance for the design of protective engineering structures, with significant engineering application value.

2.
Eur J Pharmacol ; 940: 175323, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36535492

RESUMO

Glutamine, as the most abundant amino acid in the body, participates in the biological synthesis of nucleotides and other non-essential amino acids in the process of cell metabolism. Recent studies showed that glutamine metabolic reprogramming is an important signal during cancer development and progression. This metabolic signature in cancer cells can promote the development of cancer by activating multiple signaling pathways and oncogenes. It can also be involved in tumor immune regulation and promote the development of drug resistance to tumors. In this review, we mainly summarize the role of glutamine metabolic reprogramming in tumors, including the regulation of multiple signaling pathways. We further discussed the promising tumor treatment strategy by targeting glutamine metabolism alone or in combination with chemotherapeutics.


Assuntos
Glutamina , Neoplasias , Humanos , Glutamina/metabolismo , Neoplasias/patologia , Transformação Celular Neoplásica/metabolismo , Aminoácidos , Resistência a Múltiplos Medicamentos
3.
Phytochemistry ; 163: 75-88, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31030081

RESUMO

Cyclocarya paliurus (Batalin) Iljinsk is a medicinal plant belonging to the Juglandaceae family, and its leaves are used for a traditional sweet herbal tea with bioactivity against obesity and hyperglycaemia in China. It contains various bioactive specialised metabolites, such as flavonoids, triterpenes and their glucosides, while no glycosyltransferases (GTs) have been reported in C. paliurus to date. Herein, we identified and cloned the first glucosyltransferase C. paliurus GT1. The expression profiles of C. paliurus GT1 showed very high expression in young leaves, callus and branches, but relatively low expression in old leaves and bark and no expression in root. The recombinant C. paliurus GT1 protein was heterologously expressed in Escherichia coli and exhibited catalytic activity towards multiple flavonoids favouring substrate- and regio-specific biosynthesis. Further enzyme assays indicated a preference for certain hydroxyl group glucosylation by C. paliurus GT1. C. paliurus GT1 actively catalysed the glucosylation of flavones and flavonols, but it was less active towards isoflavones, flavanones or triterpenes. C. paliurus GT1 was also able to catalyse the attachment of sugars to the thiol (S-) or amine (N-) sites on aromatic compounds but not on aliphatic compounds. Molecular docking and site-directed mutagenesis analyses indicated that A43F, V84P, and M201Y dramatically altered the regio-selectivity and activity, and the W283M mutation and deletion of the V309-D320 region enhanced the activity and the formation of disaccharides. Herein, we present the identification and characterization of the first multi-functional glucosyltransferase in C. paliurus and provide a basis for understanding the biosynthesis of flavonoid glucosides. C. paliurus GT1 could be utilized as a synthetic biology tool for the synthesis of O-, N-, or S-glucosylated natural/unnatural products.


Assuntos
Flavonoides/biossíntese , Glucosídeos/biossíntese , Glucosiltransferases/análise , Juglandaceae/química , Flavonoides/química , Glucosídeos/química , Glucosiltransferases/metabolismo , Juglandaceae/metabolismo , Estereoisomerismo , Especificidade por Substrato
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